In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain

Søgaard, Ditte; Lindblad, Maiken Marie; Paidi, Maya Devi; Hasselholt, Stine; Lykkesfeldt, Jens; Tveden‐Nyborg, Pernille

doi:10.1016/j.nutres.2014.07.004

Cited by 17 publications

(19 citation statements)

References 28 publications

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“…1(c), may be the result of a compensatory capacity protecting the brain against deficiency when general levels of VitC decrease, and could be due to both increased uptake and retention ability, but may also just reflect normal concentration-dependent changes in active transport processes. For the lowest dietary dose (100 mg VitC/kg), the decline in the CSF:plasma ratio in combination with the large CSF:brain ratio could indicate an inability to uphold sufficient concentrations of VitC to sustain the brain; a similarly low CSF:plasma ratio has been found previously in guinea pigs depleted of VitC ( 72 ) . The decreased ratio could be due to changes in the recycling mechanisms of VitC including usage of the available VitC pool in the brain, alterations of intracellular VitC reuptake, and/or changes in CSF flow rate ( 67 , 71 ) .…”

Section: Discussionsupporting

confidence: 52%

Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs

2015

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Vitamin C (VitC) deficiency is surprisingly common in humans even in developed parts of the world. The micronutrient has several established functions in the brain; however, the consequences of its deficiency are not well characterised. To elucidate the effects of VitC deficiency on the brain, increased knowledge about the distribution of VitC to the brain and within different brain regions after varying dietary concentrations is needed. In the present study, guinea pigs (like humans lacking the ability to synthesise VitC) were randomly divided into six groups (n 10) that received different concentrations of VitC ranging from 100 to 1500 mg/kg feed for 8 weeks, after which VitC concentrations in biological fluids and tissues were measured using HPLC. The distribution of VitC was found to be dynamic and dependent on dietary availability. Brain saturation was region specific, occurred at low dietary doses, and the dose -concentration relationship could be approximated with a three-parameter Hill equation. The correlation between plasma and brain concentrations of VitC was moderate compared with other organs, and during non-scorbutic VitC deficiency, the brain was able to maintain concentrations from about one-quarter to half of sufficient levels depending on the region, whereas concentrations in other tissues decreased to one-sixth or less. The adrenal glands have similar characteristics to the brain. The observed distribution kinetics with a low dietary dose needed for saturation and exceptional retention ability suggest that the brain and adrenal glands are high priority tissues with regard to the distribution of VitC.

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Section: Discussionsupporting

confidence: 52%

Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs

2015

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“…The protein extraction was performed on ten randomly chosen animals from each group as previously described [ 51 ]. Briefly, 40 mg of tissue from each of FC, Hip and Stri was dissected on ice.…”

Section: Methodsmentioning

confidence: 99%

“…The samples were denatured at 70 °C for 10 min before transfer to a 7.5% Criterion™ TGX™ Precast Midi Protein Gel, 26 well, 15 µL/well (Bio Rad, Hercules, CA, USA) and the electrophoresis was run for approximately 40 min. Afterwards the proteins were transferred to a PVDF membrane [ 51 ]. All samples were run in duplicates and normalized to total protein levels (REVERT™ Total Protein Stain, Li-Cor, Lincoln, NE, USA).…”

Section: Methodsmentioning

confidence: 99%

Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

et al. 2018

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Approximately 15% of the Western world population, including pregnant women and their children, is characterized as vitamin C (vitC) deficient. In guinea pigs, early life vitC deficiency causes spatial memory deficits, decreased hippocampal volume and neuron numbers, in otherwise clinically healthy animals. We hypothesized that vitC deficiency leads to decreased brain-derived neurotrophic factor and synaptic plasticity markers in selected brain areas (frontal cortex, hippocampus and striatum) and cause morphological changes in cornu ammonis 1 pyramidal neurons of the hippocampus either through a direct effect or indirectly by increased oxidative stress. Fifty-seven female guinea pigs were allocated to three groups receiving either 1390, 100 or 0–50 mg vitC/kg feed for 11 weeks. Dietary vitC levels were reflected in the plasma, cortical and adrenal gland levels, however, redox imbalance was only present in the adrenal glands allowing for the investigation of a direct influence of vitC deficiency on the chosen parameters in the brain. Synaptic plasticity markers were not affected in the investigated brain areas and no differences in isolated pyramidal neuron morphology was recorded. Based on our findings, it appears that vitC deficiency may primarily elicit impaired neuronal function through increased levels of oxidative stress.

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“…The protein was extracted as previously described with some modifications [ 25 ]. In short, 40 mg of frozen hippocampal tissue was excised on ice before adding 500 μL RIPA buffer (50 mmol/L tris pH 8.0, 150 mmol/L sodium chloride, 1% Triton X-100, 0.5% sodium deoxycholate and 0.1% sodium dodecyl sulfate) with 1:100 protease inhibitor cocktail (Sigma-Aldrich, Darmstadt, Germany) and 1:100 phosphatase inhibitor cocktail (Sigma-Aldrich, Darmstadt, Germany) and homogenized by mortar and pestle on ice.…”

Section: Methodsmentioning

confidence: 99%

“…The Western blotting procedure was carried out on samples in duplicates and in a randomized order, as previously described [ 25 ]. The amount of protein (determined by a dilution series) was adjusted to 11.25 μL with ultrapure water before adding 3.75 μL Laemmli buffer (Hercules, CA, USA) with 1:10 mercaptoethanol (Sigma-Aldrich, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Spatial Memory Dysfunction Induced by Vitamin C Deficiency Is Associated with Changes in Monoaminergic Neurotransmitters and Aberrant Synapse Formation

et al. 2018

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Vitamin C (vitC) is important in the developing brain, acting both as an essential antioxidant and as co-factor in the synthesis and metabolism of monoaminergic neurotransmitters. In guinea pigs, vitC deficiency results in increased oxidative stress, reduced hippocampal volume and neuronal numbers, and deficits in spatial memory. This study investigated the effects of 8 weeks of either sufficient (923 mg vitC/kg feed) or deficient (100 mg vitC/kg feed) levels of dietary vitC on hippocampal monoaminergic neurotransmitters and markers of synapse formation in young guinea pigs with spatial memory deficits. Western blotting and high performance liquid chromatography (HPLC) were used to quantify the selected markers. VitC deficiency resulted in significantly reduced protein levels of synaptophysin (p = 0.016) and a decrease in 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio (p = 0.0093). Protein expression of the N-methyl-d-aspartate receptor subunit 1 and monoamine oxidase A were reduced, albeit not reaching statistical significance (p = 0.0898 and p = 0.067, respectively). Our findings suggest that vitC deficiency induced spatial memory deficits might be mediated by impairments in neurotransmission and synaptic development.

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In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain

Cited by 17 publications

References 28 publications

Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs

Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs

Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Spatial Memory Dysfunction Induced by Vitamin C Deficiency Is Associated with Changes in Monoaminergic Neurotransmitters and Aberrant Synapse Formation

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